The regiment served in the Army of the Potomac in the Eastern Theater and was heavily engaged in the second day of fighting at the Peach Orchard outside of Gettysburg.
At the Battle of Fredericksburg, the regiment formed part of the force which engaged the Confederate right flank but lost few men.
Separated from the rest of its brigade, the regiment never received orders to withdraw and stayed in line of battle near the Peach Orchard.
Possibly because of the thick battle smoke, the regiment did not fire on the approaching brigade of Brigadier General William Barksdale.
The 141st suffered a devastating volley at close range from one of Barksdale's Mississippi regiments, and after a brief resistance withdrew towards Cemetery Ridge with a loss of almost 70% of its members.